This invention relates to a disposable unit for testing the sterility of filterable liquids by filtering the liquid using bacteriological membrane filters.
Pharmaceutical and microbiological products such as materials for intravenous or injectable medication, and microbiological media must be sold and used in sterile condition and therefore their sterility must be carefully monitored before distribution and use. Since a large number of tests must frequently be run to ensure that such products are sterile, an inexpensive, efficient, compact and accurate means of testing the sterility of filterable liquids was needed.
Two methods have been used in recent years to carry out sterility testing, the direct method and the membrane filter method which uses a membrane filter to strain the contaminants from the test liquid. In the direct method, a portion of the material to be tested for sterility is innoculated into a medium known to provide optimum conditions for the growth of the specific contaminant organism being tested. The direct method has been abandoned in recent years in favor of the membrane filter method since direct systems are somewhat limited in that they require a specific volumetric to area ratio in order to control the oxygenization of the media. Several sterility test systems using the membrane filter method are now commercially available.
The membrane filter method involves filtering a test liquid through a membrane filter having pores small enough to physically remove any contaminant microorganism from the liquid. The filter is then developed in a growth media to determine if any contaminant microorganisms were present in the test liquid.
The MILLIPORE.RTM..sup.1 filter is an example of a recently developed bacteriological membrane filter. These are filters which consist of stabilized dry, cellulose ester gel membranes about 0.005 inches thick which are supplied as discs or sheets of varying diameters and shapes. These membrane filters are true absolute filters and depend entirely on a sieving action for their effectiveness. In using these membrane filters, it is necessary to know the nature of the organism to be removed. The smallest dimension of the organism to be removed must be greater than the membrane pore size. Tables of characteristic dimension of a wide range of microorganisms and viruses are available in the scientific literature. FNT 1 MILLIPORE is the registered trademark of Millipore Corporation, Bedford, Mass.
The membrane filter method is conveniently used in liquid sterility test units since the liquids to be tested can easily be filtered using membrane filters, for example Millipore filters. For accurate and reproducible sterility test results, secondary contamination from outside sources must be minimized. For this reason these tests are usually carried out in a clean bench area, for example in a laminar flow hood which eliminates all particles above 0.5.mu. in diameter. In addition, it is important that handling of the filter membranes be kept to a minimum. The recently developed sterility test systems are designed so that the membrane need not be removed from the test unit in order to be developed.
A liquid sample is tested for sterility in the systems employing the membrane filtration method by filtering the test liquid through the system's test unit. The test unit is rinsed with a suitable sterile solution to remove any residue of the product material retained on the filter and the outlet port is sealed. The unit is filled with a culture medium and the test unit is incubated. Lack of sterility of the test liquid is indicated by turbidity in the medium indicating the presence of contaminants in the liquid tested.
This method is to be contrasted with earlier sterility units and sterility systems in which after the test sample had been filtered the filter membrane was removed from the test unit, divided into sections and each section was incubated in a culture media. This two-step procedure was cumbersome and increased the chances of secondary contamination and is therefore less desirable than systems using single filtration-incubation sterility test units.
Examples of some recently developed systems having filtration-incubation sterility test units herein sometimes referred to as sterility test units or units are described in U.S. Pat. No. 4,036,698 issued July 19, 1977, the Steritest Sterility Testing System marketed by Millipore Corp., the disposable sterile membrane filter unit available from Arthur H. Thomas, Philadelphia, Penn., and the Sartorius Membranfilter Sterility Testing System available from Sartorius Filters, Inc., Cherry Hill, N.J. The test units in these systems overcome many of the drawbacks of previous two-step sterility test units, in that filtration and incubation take place in the same unit, but several problems remain. These commercially available test units lack a convenient method of internally sealing the outlet port of the unit prior to the introduction of the incubation culture medium. In addition, since multiple sterility tests are often run simultaneously, the presently available filtration-incubation sterility test units require considerable hood space since they must be set up side by side.